PERSONAL HEALTH; Small Advances Against Pancreatic Cancer

By JANE E. BRODY

Published: June 8, 2010

Rarely is it said that someone is lucky to have had cancer. But Justice Ruth Bader Ginsburg of the Supreme Court might be one such person.

Justice Ginsburg was treated successfully for colon cancer in 1999 and is examined each year at the National Institutes of Health, where in January 2009 a routine CT scan revealed a very small cancer in the center of her pancreas.

While the life expectancy for most people found to have pancreatic cancer is usually a year or less, Justice Ginsburg has apparently been well after she recovered from surgery to remove the tumor, about the smallest that can be detected by a CT scan -- one centimeter, or less than half an inch, wide.

A Challenging Disease

Pancreatic cancer has proved to be one of the most challenging malignant diseases, the 11th-most-common cause of cancer but the fourth-leading cause of cancer deaths. It affects a life-sustaining organ that sits atop the stomach in the center of the abdomen, where cancer can develop and spread before it produces recognizable symptoms.

The disease is detected and treated at a potentially curable stage in fewer than 20 percent of patients. For that reason, its overall five-year survival rate is less than 5 percent.

Pancreatic cancer will be diagnosed in about 42,000 people this year in the United States; some 35,000 people will die of it. It is primarily a disease of older people, with 90 percent of cases occurring in those over 55 and 80 percent in those over 65.

The disease became increasingly common in the last half century as cigarette smoking rose in popularity. Toxic chemicals in cigarette smoke and smokeless tobacco are thought to cause a gradual accumulation of gene mutations that allow cancer cells to form and spread rapidly; users have two to three times the risk of developing pancreatic cancer. Only now has a slight decline in incidence begun, thanks to the recent drop in smoking rates.

Other risk factors include obesity, Type 2 diabetes and lack of physical exercise, as well as occupational exposure to certain pesticides, dyes and chemicals used in metal refining. Less well-defined risks include chronic pancreatitis, cirrhosis of the liver, gallbladder removal, heavy alcohol consumption, a diet high in fat and cholesterol and, possibly, infection with the hepatitis B virus.

Men and women are equally at risk, although there are somewhat more cases among men, probably because more men smoked. The disease is also more common among African-Americans than whites, partly because black men have higher rates of smoking and diabetes, and black women higher rates of obesity.

A Genetic Component

Five to 10 percent of pancreatic cancer patients have a family history of the disease and are presumed to carry mutations that impair their body's ability to repair damage to DNA. Several such mutations have been identified and linked to an increased risk of developing pancreatic cancer. In families where four or more members have had the disease, the risk to others in the family can be as high as 57 times that of people with no such family history, Dr. Manuel Hidalgo of Johns Hopkins University School of Medicine reported in April in The New England Journal of Medicine.

In a rare hereditary example, researchers led by Dr. Teresa A. Brentnall of the University of Washington School of Medicine described a family in which nine blood relatives had died of pancreatic cancer, some at young ages. Through detailed molecular detective work, they identified a mutation in a gene called Palladin in all those with cancer or precancer of the pancreas that was lacking in other family members. A still-healthy relative with this mutation chose to have his pancreas removed when it was found to harbor precancerous changes, and he has remained cancer-free for more than 14 years.

In an interview, Dr. Brentnall said that unraveling how the Palladin mutation works helped explain why this cancer is usually so deadly. ''Pancreatic cancer cells are surrounded by a dense layer of fibroblasts,'' she said, adding that in nonfamilial pancreatic cancer, the Palladin protein ''makes the fibroblasts grow little feet filled with poisonous enzymes that create holes through which the cancer cells can escape and invade blood vessels very early in the disease, before the tumor is of significant size.''

Thus, the cancer is typically metastatic and incurable by the time it is diagnosed.

Adding to the problem of early diagnosis is the lack of a reliable screening test and the vagueness of early symptoms, if any. Without a family history that might prompt a doctor to suspect pancreatic cancer, patients are often first checked for problems like chronic reflux, gallbladder disease and bowel disorders.

For those with a family history of pancreatic cancer, Dr. Brentnall and other experts at leading medical centers now offer screening tests, including an endoscopic ultrasound exam, to look for abnormalities in the pancreas that may herald precancerous changes. But such exams are not cost-effective screening tools for the general population.

As with patients with the Palladin mutation, those on the verge of developing cancer are offered surgery to remove the pancreas, which results in diabetes and a lifetime dependence on daily insulin injections.

Dr. Eileen M. O'Reilly, a pancreatic cancer expert at Memorial Sloan-Kettering Cancer Center in New York, says there are six or seven known genetic factors involved in pancreatic cancer, including the BRCA1 and BRCA2 mutations more commonly associated with an increased risk of cancers of the breast, ovary, colon and prostate. Screening might also be considered in families with such traits, she said, as well as in the much larger number of families, like the family of former President Jimmy Carter, in which the genetic link is not known. Mr. Carter's father, mother, two sisters and brother were afflicted.

A Hint of Progress

Dr. James L. Abbruzzese of the M. D. Anderson Cancer Center in Houston said some progress had been made in treating the disease. Radical surgery, called the Whipple operation, remains the mainstay of therapy, but only a small minority of patients -- whose cancers have not yet invaded surrounding blood vessels -- have traditionally been eligible for surgery.

Now, he explained, 10 to 20 percent more patients can undergo surgery after receiving treatment with radiation and chemotherapy to reduce the extent of disease, enabling the surgeon to remove the cancer and be sure the tissue around it is cancer-free.

However, Dr. Abbruzzese said, ''many still have lymph node involvement'' that leads to eventual spread of the disease. ''We still need to identify better systemic therapies'' to attack these escaping cancer cells.

''The median survival for surgical patients is two to three years, with maybe 10 to 15 percent who live longer,'' he said. ''It's not a home run yet.''

PHOTO: SURVIVOR: Justice Ruth Bader Ginsburg at New York University in April. (PHOTOGRAPH BY MARY ALTAFFER/ASSOCIATED PRESS)